CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival
CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival
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DOI：
10.1038/modpathol.2009.186
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发表时间：
2010-04-01
期刊：
影响因子：
7.5
通讯作者：
Dacic, Sanja
中科院分区：
文献类型：
--
作者：
Krasinskas, Alyssa M.;Bartlett, David L.;Dacic, Sanja
CDKN2A (p16) 纯合缺失是胸膜间皮瘤最常见的遗传改变之一，发生率高达 74%。 MTAP 位于 9p21 区域的同一基因簇中，并且在大多数 CDKN2A 缺失病例中被共同缺失。这项研究检查了腹膜间皮瘤的遗传改变，腹膜间皮瘤可能具有与胸膜间皮瘤不同的发病机制。对一式三份的组织微阵列中的 26 例腹膜间皮瘤进行了研究。使用 CDKN2A 和 MTAP 位点特异性探针进行双色荧光原位杂交。 26 例腹膜间皮瘤中有 9 例 (35%) 存在 CDKN2A 纯合缺失； MTAP 在每种情况下都被共同删除。所有 CDKN2A 缺失的病例均出现 p16 蛋白表达缺失； 5 例 p16 蛋白缺失，但没有 CDKN2A 缺失的证据。所有具有 CDKN2A 缺失的患者均为男性（P，NS），并且比无缺失的患者（平均 52 岁）显着年长（平均 63 岁）（P - 0.033，t 检验）。本研究无法证明与石棉暴露之间的关联。与胸膜间皮瘤类似，CDKN2A 缺失和 p16 蛋白表达缺失的患者总体生存率和疾病特异性生存率较差（分别为 P = 0.010 和 0.006；Kaplan-Meier 对数等级）。腹膜间皮瘤中 CDKN2A-MTAP 共缺失的检测，加上 p16 免疫组织化学染色作为一种廉价的筛查工具，可以帮助识别那些在积极的细胞减灭手术联合腹腔热灌注化疗后可能出现不良结果的患者，以及那些可能对 MTAP 途径的靶向治疗有反应的患者。现代病理学(2010) 23, 531-538; doi:10.1038/modpathol.2009.186； 2010 年 1 月 15 日在线发布
Homozygous deletion of CDKN2A (p16) is one of the most common genetic alterations in pleural mesotheliomas, occurring in up to 74% of cases. MTAP resides in the same gene cluster of the 9p21 region and is co-deleted in the majority of CDKN2A deleted cases. This study examines the genetic alterations in peritoneal mesotheliomas, which may have a different pathogenesis than their pleural counterparts. Twenty-six cases of peritoneal mesotheliomas in a triplicate tissue microarray were studied. Dual-color fluorescence in situ hybridization was performed with CDKN2A and MTAP locus-specific probes. Nine of 26 (35%) peritoneal mesotheliomas had homozygous deletion of CDKN2A; MTAP was co-deleted in every case. All cases with CDKN2A deletions had loss of p16 protein expression; five cases had loss of p16 protein without evidence of CDKN2A deletions. All patients with CDKN2A deletions were men (P, NS) and were significantly older (mean, 63 years) than the patients with no deletions (mean, 52 years) (P - 0.033, t-test). An association with asbestos exposure could not be proved in this study. Similar to pleural mesotheliomas, patients with CDKN2A deletions and loss of p16 protein expression had worse overall and disease-specific survival (P = 0.010 and 0.006, respectively; Kaplan-Meier log rank). Detection of CDKN2A-MTAP co-deletion in peritoneal mesotheliomas, coupled with a p16 immunohistochemical stain as an inexpensive screening tool, can help identify those patients who may have an unfavorable outcome after aggressive cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and those who may respond to targeted therapy of the MTAP pathway. Modern Pathology (2010) 23, 531-538; doi:10.1038/modpathol.2009.186; published online 15 January 2010